Do Genes Affect Who Develops Treatment-Resistant Depression?

Depression is one of the most common mental health conditions worldwide. For many people, antidepressants and therapy can provide meaningful relief. But for some—those with treatment-resistant depression (TRD)—standard treatments do not work, even after trying multiple options. This raises an important question: why do some people respond while others do not?

A new study published in Neuropsychopharmacology explored how genetics may contribute to TRD, comparing patterns between East Asian and European populations.

Why Look at Genetics?

Genes influence how our brains function, how we respond to stress, and even how we metabolize medications. Studying genetic “signatures” may help explain why specific individuals are more likely to develop TRD and point toward new ways to personalize treatment.

Until now, most genetic studies of TRD have been done in people of European ancestry. This study helps close that gap by also incorporating large-scale data from the Taiwan Biobank and comparing the results with those of the U.S. All of Us Research Program.

What the Study Found

• Personality-linked genes matter: Genetic markers tied to traits like nervousness, worry, and emotional sensitivity were consistently linked to higher TRD risk in East Asian participants.
• Some risks are shared: Many genetic patterns linked to TRD were seen in both East Asian and European groups.
• Some risks differ by population: Certain genetic factors related to education, cognition, and temperament were significant in Europeans but not in East Asians, and vice versa.
• Strong evidence: These findings were consistent across different definitions of TRD, adding confidence to the results.

Why It Matters for Patients

This research shows that while some genetic risks for TRD are universal, others are population-specific. That means people of different ancestries may face different biological risk factors. Studying diverse populations is crucial to ensure that future treatments are inclusive and effective for all individuals.

As psychiatry advances toward precision medicine, genetic insights like these may one day help match patients with the therapies most likely to work for them—reducing trial and error and bringing relief sooner.

Reference

Cheng C-F, Kao W-Y, Lin M-C, Su M-H, Wu C-S, Fan C-C, Wang S-H. Comparative polygenic predispositions of treatment-resistant depression in East Asian and European populations. Neuropsychopharmacology. 2025. doi:10.1038/s41386-025-02242-9

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Disclaimer:
This article was created with the help of artificial intelligence (AI) to improve clarity and readability. All medical content has been carefully reviewed and approved by Joao L. de Quevedo, MD, PhD, Director, UTHealth Houston Center for Interventional Psychiatry. This information is provided for educational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment.

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